Twenty patients (16 from 2-16 years old, mean 10.4 years; 4 from 17-69, mean 47.5 years) with an encephalitis lethargica (EL) syndrome resembling that reported in the 1916-1927 epidemic, and presenting between 1999 and 2002, are reported from Great Ormond Street Hospital, London, and other tertiary neurology centers in the UK. The EL syndrome consisted of a sleep disorder (somnolence, sleep inversion, or insomnia), lethargy, parkinsonism, dyskinesia (dystonia, oculogyric crises, hemiballism, chorea or tics), and neuropsychiatric symptoms (mutism (10 patients), anxiety, depression (6), agitation, catatonia, obsessive-compulsive disorder, ophthalmoplegia or pupillary abnormalities (7), headache (6), and seizures (3). Eleven patients (55%) had a pharyngitis infection before onset of symptoms, 10 had a monophasic illness, and 7 a relapsing course. Five made a complete recovery at mean follow-up of 5 months (range 2-14 months), and 15 have persistent impairments (movement disorder in 6 and neuropsychiatric illness in 10). CSF was abnormal in 13 of 16 tested (elevated protein [>0.3 g/dl] in 75%, and oligoclonal bands in 69%). MRI was abnormal in 40%, with inflammatory changes localized to the basal ganglia, midbrain and thalamus. ASOT was elevated in 65% and normal in 35%; 2 had positive throat cultures for group A b-hemolytic Streptococcus. Western immunoblotting showed autoantibodies reactive against human basal ganglia antigens in 95% of EL patients compared to 2-4% of child and adult controls (P<0.0001); they were also present in the CSF of 4 EL patients. Immunohistochemistry localized antibody binding to neurons. This EL-like syndrome appears to be secondary to a postinfectious autoimmunity against deep grey matter neurons. [1]

COMMENT. This report of an encephalitis lethargica (EL) syndrome, with similar characteristics to that of von Economo’s EL first described in 1916, may now be added to the growing list of immune-mediated movement and neuropsychiatric disorders linked to group A streptococcal infections. Sydenham’s chorea is the classic phenotype and more recently, pediatric autoimmune neuropsychiatric disorder (PANDAS) and post-streptococcal dystonia (Dale et al, 2001). That anti-basal ganglia antibodies are pathogenic in this spectrum of autoimmune disorders is suggested but not yet proven. Questions regarding the regional specificity of the antibodies, and the possibility that they may be markers for a destructive process, secondary to T cell-mediated or direct toxicity from the streptococcus infection, need to be clarified [2]. A response of EL to plasma exchange or other immunotherapies (Blunt et al, 1997), as sometimes reported in PANDAS, would be of interest. Behavior disorders, resembling those of attention-deficit-hyperactivity and oppositional defiant disorders, and termed ’organic drivenness,’ were described as complications of encephalitis following the influenza pandemic of 1918 (Hohman, Ebaugh, 1922, 1923; Kahn, Cohen, 1934).